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Intrahepatic mRNA expression in hepatitis C virus and HIV/hepatitis C virus co-infection: infiltrating cells, cytokines, and influence of HAART

Kuntzen, Thomasa,b; Tural, Cristinad; Li, Bina; Feldmann, Georgb; Kupfer, Berndc; Nischalke, Hans Dieterb; Clotet, Bonaventurad; Sauerbruch, Tilmanb; Rockstroh, Juergen Kb; Spengler, Ulrichb

doi: 10.1097/QAD.0b013e3282f3553b
Basic Science: Concise Communications

Objective: Liver disease is more progressive in HIV/hepatitis C virus (HCV) co-infection than in HCV infection alone. This accelerated pathogenesis is probably influenced by differences in the composition of infiltrating inflammatory cells and the local release of inflammatory and profibrogenic cytokines.

Methods: Using quantitative real-time reverse transcriptase–polymerase chain reaction (qRT-PCR) we studied intrahepatic messenger RNA levels of cytokines and cellular markers defining distinct subsets of inflammatory cells in liver biopsies from 33 HCV-mono-infected and 40 HIV/HCV-co-infected patients.

Results: Despite their well preserved peripheral blood CD4 cell counts (median 598 cells/μl), HIV/HCV-co-infected patients displayed significantly lower CD4 mRNA levels than HCV-mono-infected patients, whereas increased mRNA levels of CD3ϵ, TCRα, CD8α and CD8β suggested intrahepatic enrichment of CD8 T cells in HIV co-infection. Intrahepatic mRNA levels of the inflammatory cytokines interferon gamma (IFN-γ), regulated upon activation, normal T-cell expressed and secreted (RANTES, CCL5), macrophage inflammatory protein 1 alpha (CCL3) and interferon-inducible protein 10 (CXCL10) were significantly higher in HIV-positive than in HIV-negative patients, whereas mRNA levels of the profibrogenic cytokines macrophage chemoattractant protein 1 (CCL2), secondary lymphochemokine (CCL21) and stroma-derived factor 1 (CXCL12) did not differ between the two groups. All changes were less pronounced in the subgroup of HIV-positive patients receiving antiretroviral treatment (HAART) than in untreated HIV-positive patients.

Conclusion: The accelerated liver disease observed in HIV/HCV-co-infected patients might reflect enhanced intrahepatic inflammatory responses rather than increased local transcription of directly profibrogenic cytokines.

From the aPartners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA

bDepartment of Internal Medicine I, University Hospital of Bonn, Bonn, Germany

cInstitute for Medical Microbiology, Immunology, and Parasitology, University Hospital of Bonn, Bonn, Germany

dClinical HIV Unit and Irsicaixa Foundation, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Barcelona, Spain.

Received 15 December, 2006

Revised 2 October, 2007

Accepted 9 October, 2007

Correspondence to Thomas Kuntzen, MD, Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, 149 13th street, 6th floor, Room 6624, Charlestown, MA 02129, USA. Tel: +1 617 643 2838; fax: +1 617 726 5411; e-mail: tkuntzen@partners.org

© 2008 Lippincott Williams & Wilkins, Inc.